CN103142591A - Ticarcillin sodium-potassium clavulanate pharmaceutical composition powder injection - Google Patents
Ticarcillin sodium-potassium clavulanate pharmaceutical composition powder injection Download PDFInfo
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- CN103142591A CN103142591A CN2013100747227A CN201310074722A CN103142591A CN 103142591 A CN103142591 A CN 103142591A CN 2013100747227 A CN2013100747227 A CN 2013100747227A CN 201310074722 A CN201310074722 A CN 201310074722A CN 103142591 A CN103142591 A CN 103142591A
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- metronidazole
- ticarcillin sodium
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- clavulanate
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Abstract
The invention provides a ticarcillin sodium-potassium clavulanate pharmaceutical composition powder injection, relating to the field of a medicinal preparation and a preparation method thereof. The invention mainly solves the problems of high dosage of single ticarcillin sodium, potassium clavulanate and metronidazole preparation, poor treatment effect after combination, and great side effect in the prior art. The pharmaceutical composition comprises ticarcillin sodium-potassium clavulanate and metronidazole lipid microspheres in a weight ratio of 100:1-100:5, wherein the weight of the metronidazole lipid microspheres is metered on the basis of metronidazole; and when the pharmaceutical composition is prepared into a powder injection, the pH value of the water solution of the pharmaceutical composition is 7.0-9.0. The pharmaceutical composition powder injection provided by the invention has high curative effect, and can reduce the consumption of the metronidazole by more than 80%, thereby greatly relieving or avoiding the toxic and side effects of the metronidazole, especially digestive tract reactions, including nausea, vomit, inappetence, abdominal colic and neurotoxicity, and lowering the incidence rate of adverse reactions.
Description
Technical field:
The present invention relates to pharmaceutical preparation and preparation method field, relate in particular to a kind of injection ticarcillin sodium potassium clavulanate composition injectable powder and preparation method thereof.
Background technology:
The Main Ingredients and Appearance of injection ticarcillin sodium and clavulanate potassium is ticarcillin sodium and clavulanate potassium.Ticarcillin is the penicillins wide-spectrum bactericide, and clavulanic acid is the efficient beta-lactamase inhibitor of a kind of irreversibility.Multiple gram positive bacteria (G) and negative bacterium (G) can produce beta-lactamase, and this fermentoid can be with its destruction before penicillin medicine acts on pathogen.Clavulanic acid destroys the defensive barrier of antibacterial by the blocking-up beta-lactamase, recovers ticarcillin sensitivity.The independent antibacterial action of clavulanate potassium is very little, but with the ticarcillin compatibility after this product is become have the antibiotic of broad-spectrum bactericidal action, be applicable to the experiential therapy of bacterial infection disease widely.
1972, Tally found that first metronidazole has the effect of whole body anaerobe resistant, and was defined as the drug of first choice of anti anaerobic bacteria infection by World Health Organization (WHO) in 1978.In clinical extensive use, its purposes is widened day by day along with first nitre, and its advantage is: the scope of anaerobe resistant is wide, and sterilizing power is strong, and general avirulence has no drug resistance.It has tablet, injection, suppository, compound preparation, can be for oral, quiet notes and anus plug, also can be applied to intravenously administrable with other multiple antibacterials preparation, so, the requisite a kind of curative of clinical departments become.Recently studying its mechanism of action is, answers by its reduzate and bacterial cell DNA antisense, disturbs growth, the breeding of antibacterial, last kill bacteria.
Untoward reaction appears in nearly 15-30% case clinically, and is the most common with digestive tract reaction, comprises nauseating, vomiting, inappetence, abdominal colic, generally do not affect treatment; Neurological symptom has headache, dizzy, abnormal, the numb limbs and tense tendons of occasionally feeling, ataxia, polyneuritis etc., and heavy dose can cause tic.In the measles such as minority case generation, flushing, pruritus, cystitis, dysuria, mouth, metallic taste and leukopenia etc., all belong to reversibility, recovers voluntarily after drug withdrawal, and reviewing analysis shows that the main cause that untoward reaction occurs is the overdose medication.
infection in clinical operation usually is accompanied by the mixed infection that contains anaerobe and aerobe, rather than the infection of single anaerobe or aerobe, it is the clinical first-selected medication for the treatment of anaerobic infection because of metronidazole, ticarcillin sodium and clavulanate potassium commonly used and metronidazole drug combination contain the MOI of anaerobe for preventing post-operation infection and treatment clinically, but injection ticarcillin sodium and clavulanate potassium and injection metronidazole are all as single product, during the difference medication, the consumption of metronidazole is very large, the toxic and side effects of metronidazole is very strong, the metronidazole of normal therapeutic dosage can produce digestive tract reaction, the most common comprise nauseating, vomiting, inappetence, abdominal colic and higher neurotoxicity.To this for clinical provide a kind of safe and effective, medicine that toxic and side effects is low is extremely urgent, Given this, proposes the present invention.
Summary of the invention:
Technical problem to be solved by this invention is to overcome the defective of prior art, provide a kind of curative effect high, safe, good stability, the ticarcillin sodium potassium clavulanate composition that toxic and side effects is low, the principal agent of this pharmaceutical composition is: ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere, said composition can effectively be treated the MOI that contains anaerobe.
Technical problem to be solved by this invention realizes by the following technical solutions.
A kind of ticarcillin sodium potassium clavulanate composition, it is characterized in that, this pharmaceutical composition comprises ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere, the weight ratio of ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere is 100:1-100:5, the weight of metronidazole lipid microsphere is in metronidazole, this pharmaceutical composition is prepared into powder ampoule agent for injection, and the pH value of the aqueous solution of this pharmaceutical composition is 7.0-9.0.
In this pharmaceutical composition, the preferred weight ratio of ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere is 100:3, and the weight of metronidazole lipid microsphere is in metronidazole, and the preferred pH value of the aqueous solution of this pharmaceutical composition is 7.8-8.5.
Another object of the present invention is to provide a kind of method that ticarcillin sodium potassium clavulanate composition is prepared into powder ampoule agent for injection, it is characterized in that, the concrete steps of the method are:
(1) preparation metronidazole lipid microsphere, this goods mean diameter is less than 120nm, and pH value is between 7.8 ~ 8.5, and the absolute value of Zeta-potential is greater than 20mV, and envelop rate is more than 80%.
The crude drug component of preparation metronidazole lipid microsphere is:
The step of preparation metronidazole lipid microsphere is:
A) glycerol for injection and the poloxamer F-68 with recipe quantity is dissolved in water for injection, be placed in 80 ℃ of water bath with thermostatic control magnetic stirring apparatuss and be stirred to whole dissolvings, make mixture A, the injection water yield can be with abundant fused the getting final product of glycerol for injection and poloxamer F-68;
B) recipe quantity oleic acid is added in the oil phase that is consisted of by long-chain fat acid glyceride and medium chain length fatty acid triglyceride, forms and mix oil phase;
C) fabaceous lecithin and the metronidazole with recipe quantity adds in dehydrated alcohol 200ml, is stirred to fabaceous lecithin and metronidazole under 80 ℃ all after dissolving, and decompression volatilizes dehydrated alcohol, then adds the mixing oil phase, stirs and makes mixture B;
D) mixture A is added in mixture B, be placed in the 8000r/min of high-speed tissue mashing machine and stir 3 times, each 3min;
E) regulate pH value to 7.8-8.5, water for injection is settled to 1000ml, adds in high pressure homogenizer 70MPa homogenizing 8 times;
F) bottling, gland, 100 ℃ of sterilization 30min, the rapid cooling of ice-water bath and get final product, standby;
(2) ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere are dropped into respectively in the efficient asymmetric mixer of V-type in proportion, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing;
(3) will add in racking machine through ticarcillin sodium and clavulanate potassium and the metronidazole lipid microsphere mixed material of outer cleaning/disinfecting, adjust loading amount according to batch production ordering, be distributed into cillin bottle, buckle butyl rubber plug, namely get the ticarcillin sodium potassium clavulanate composition injectable powder of injection through rolling lid, lamp inspection, packing.
The specification that described ticarcillin sodium potassium clavulanate composition is prepared into powder ampoule agent for injection is 1.6g/ bottle or 3.2g/ bottle, by the ticarcillin sodium and clavulanate.
Pharmaceutical composition preparation technology of the present invention is simple, has guaranteed well the growth of related substance in the storage of the stability of active component and finished product.
The present invention is directed to treatment clinically and contain the MOI of anaerobe and propose, the agent of a kind of injection ticarcillin sodium and clavulanate potassium composition powder injection is provided.The every consumption per day of ticarcillin sodium and clavulanate potassium list product preparation adult is the 9.6g left and right clinically, and the consumption that metronidazole list product preparation is grown up every day is the 2g left and right.in ticarcillin sodium potassium clavulanate composition provided by the invention, the ticarcillin sodium and clavulanate potassium, metronidazole lipid microsphere (take metronidazole) weight ratio (W/W) is 100:1-100:5, therefore ticarcillin sodium and clavulanate potassium consumption every day is 9.6g, when dividing 3 administrations, the consumption of metronidazole every day is 96mg-480mg, each consumption is 32mg-160mg, be that 4000ml calculates by the normal adult total blood volume, after each administration, blood drug level is 8-40 μ g/ml, and the metronidazole effective blood drug concentration is 2-8 μ g/ml, the metronidazole lipid microsphere has slow releasing function, the effective blood drug concentration time can keep more than 12 hours in vivo.Pharmaceutical composition injectable powder provided by the invention not only has high curative effect thus, and can reduce metronidazole consumption (using more than 80% less), thereby greatly alleviate or avoided the toxic and side effects of metronidazole, digestive tract reaction particularly, comprise nauseating, vomiting, inappetence, abdominal colic and neurotoxicity, more reduced the incidence rate of untoward reaction.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect is easy to understand, below in conjunction with specific embodiment, further set forth the present invention.
For the concordance of guarantee test result, the embodiment of the present invention has been used raw material, adjuvant, cillin bottle and the plug of same batch, and has adopted consistent production technology to prepare the ticarcillin sodium potassium clavulanate composition injectable powder of injection.
Embodiment one, the agent of injection ticarcillin sodium and clavulanate potassium composition powder injection are in 1000
Prescription (specification: the 1.6g/ bottle):
Ticarcillin sodium and clavulanate potassium 1600g
Metronidazole lipid microsphere (in metronidazole) 48g
Preparation technology:
Ticarcillin sodium and clavulanate potassium, the metronidazole lipid microsphere (in metronidazole) of recipe quantity are dropped into respectively in the efficient asymmetric mixer of V-type in proportion, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing; To add in racking machine through ticarcillin sodium and clavulanate potassium and the metronidazole lipid microsphere mixed material of outer cleaning/disinfecting, adjust loading amount according to batch production ordering, be distributed into cillin bottle, buckle butyl rubber plug, namely get the ticarcillin sodium potassium clavulanate composition injectable powder of injection through rolling lid, lamp inspection, packing.
Embodiment two, the agent of injection ticarcillin sodium and clavulanate potassium composition powder injection are in 1000
Prescription (specification: the 3.2g/ bottle):
Ticarcillin sodium and clavulanate potassium 3200g
Metronidazole lipid microsphere (in metronidazole) 96g
Preparation technology:
Ticarcillin sodium and clavulanate potassium, the metronidazole lipid microsphere (in metronidazole) of recipe quantity are dropped into respectively in the efficient asymmetric mixer of V-type in proportion, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing; To add in racking machine through ticarcillin sodium and clavulanate potassium and the metronidazole lipid microsphere mixed material of outer cleaning/disinfecting, adjust loading amount according to batch production ordering, be distributed into cillin bottle, buckle butyl rubber plug, namely get the ticarcillin sodium potassium clavulanate composition powder pin of injection through rolling lid, lamp inspection, packing.
Clinical data
In the patient who makes a definite diagnosis anaerobe and aerobe (to the aerobe of ticarcillin sodium and clavulanate potassium sensitivity) mixed infection, use A scheme (3 bottles/day of injection ticarcillin sodium and clavulanate potassium composition powder injections (3.2g/ bottle)) and B scheme (ticarcillin sodium and clavulanate potassium 9.6g/ day+metronidazole 2g/ day) GP TH, each is organized and divides equally 3 venoclysises every day, and its curative effect and untoward reaction are as follows:
Total number of cases 35 examples of A scheme group, effective 33 examples, total effective rate is total number of cases 35 examples of 94.2%, B scheme group, effective 31 examples, total effective rate is 88.6%.
Adverse effect
Treat in 70 routine cases, the untoward reaction of varying degree appears in totally 13 examples, the untoward reaction rate is 18.6%, wherein gastrointestinal reaction appears in the routine patient of A scheme group 3, show as nauseating, vomiting, the side effect incidence rate be 8.6%, B scheme group totally 10 examples the untoward reaction of varying degree appears, the side effect incidence rate is 28.6%, it is nauseating to show as, vomiting, inappetence, headache, dizzy.A scheme group adverse reaction rate and degree are all lower than B scheme group.
Above demonstration and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (4)
1. ticarcillin sodium potassium clavulanate composition, it is characterized in that, this pharmaceutical composition comprises ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere, the weight ratio of ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere is 100:1-100:5, the weight of metronidazole lipid microsphere is in metronidazole, this pharmaceutical composition is prepared into powder ampoule agent for injection, and the pH value of the aqueous solution of this pharmaceutical composition is 7.0-9.0.
2. ticarcillin sodium potassium clavulanate composition according to claim 1, it is characterized in that, in this pharmaceutical composition, the preferred weight ratio of ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere is 100:3, the weight of metronidazole lipid microsphere is in metronidazole, and the preferred pH value of the aqueous solution of this pharmaceutical composition is 7.8-8.5.
3. the described pharmaceutical composition of claim 1 or 2 is prepared into the method for powder ampoule agent for injection, it is characterized in that, the concrete steps of the method are:
(1) preparation metronidazole lipid microsphere
The crude drug component of preparation metronidazole lipid microsphere is:
The step of preparation metronidazole lipid microsphere is:
A) glycerol for injection and the poloxamer F-68 with recipe quantity is dissolved in water for injection, be placed in 80 ℃ of water bath with thermostatic control magnetic stirring apparatuss and be stirred to whole dissolvings, make mixture A, the injection water yield can be with abundant fused the getting final product of glycerol for injection and poloxamer F-68;
B) recipe quantity oleic acid is added in the oil phase that is consisted of by long-chain fat acid glyceride and medium chain length fatty acid triglyceride, forms and mix oil phase;
C) fabaceous lecithin and the metronidazole with recipe quantity adds in dehydrated alcohol 200ml, is stirred to fabaceous lecithin and metronidazole under 80 ℃ all after dissolving, and decompression volatilizes dehydrated alcohol, then adds the mixing oil phase, stirs and makes mixture B;
D) mixture A is added in mixture B, be placed in the 8000r/min of high-speed tissue mashing machine and stir 3 times, each 3min;
E) regulate pH value to 7.8-8.5, water for injection is settled to 1000ml, adds in high pressure homogenizer 70MPa homogenizing 8 times;
F) bottling, gland, 100 ℃ of sterilization 30min, the rapid cooling of ice-water bath and get final product, standby;
(2) ticarcillin sodium and clavulanate potassium and metronidazole lipid microsphere are dropped into respectively in the efficient asymmetric mixer of V-type in proportion, mix after 1.5 hours, listen by the aluminum that drain hole is put into after sterilization; Aluminum is listened rolled lid, labeling, packing;
(3) will add in racking machine through ticarcillin sodium and clavulanate potassium and the metronidazole lipid microsphere mixed material of outer cleaning/disinfecting, adjust loading amount according to batch production ordering, be distributed into cillin bottle, buckle butyl rubber plug, namely get the ticarcillin sodium potassium clavulanate composition injectable powder of injection through rolling lid, lamp inspection, packing.
4. ticarcillin sodium potassium clavulanate composition according to claim 3 is prepared into the method for powder ampoule agent for injection, it is characterized in that: the specification that described ticarcillin sodium potassium clavulanate composition is prepared into powder ampoule agent for injection is 1.6g/ bottle or 3.2g/ bottle, by the ticarcillin sodium and clavulanate.
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| CN2013100747227A CN103142591A (en) | 2013-03-08 | 2013-03-08 | Ticarcillin sodium-potassium clavulanate pharmaceutical composition powder injection |
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| CN2013100747227A CN103142591A (en) | 2013-03-08 | 2013-03-08 | Ticarcillin sodium-potassium clavulanate pharmaceutical composition powder injection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114159432A (en) * | 2020-09-11 | 2022-03-11 | 成都倍特药业股份有限公司 | Ticarcillin sodium and potassium clavulanate pharmaceutical composition and preparation method thereof |
-
2013
- 2013-03-08 CN CN2013100747227A patent/CN103142591A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| 冯大林 等: "脂质微球给药系统的研究进展", 《现代医药卫生》 * |
| 沈学坤 等: "278例阑尾炎手术抗菌药物合理使用分析", 《中国药业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114159432A (en) * | 2020-09-11 | 2022-03-11 | 成都倍特药业股份有限公司 | Ticarcillin sodium and potassium clavulanate pharmaceutical composition and preparation method thereof |
| CN114159432B (en) * | 2020-09-11 | 2024-01-09 | 成都倍特药业股份有限公司 | Tebucillin sodium clavulanate potassium pharmaceutical composition and preparation method thereof |
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Application publication date: 20130612 |